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Transition-state stabilization in the mechanism of tyrosyl-tRNA synthetase revealed by protein engineering.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Leatherbarrow, R. W. Fersht, A. R. Winter, Greg |
| Copyright Year | 1985 |
| Abstract | The principal catalytic factor in the activation of tyrosine by the tyrosyl-tRNA synthetase is found to be improved binding of ATP in the transition state. The activation reaction involves the attack of the tyrosyl carboxylate on the alpha-phosphate group of ATP to generate a pentacoordinate transition state. Model building of this complex located a binding site for the gamma-phosphate group of ATP, consisting of hydrogen bonds with the side chains of Thr-40 and His-45. Removal of these groups by protein engineering shows that they contribute no binding energy with unreacted ATP but put all of their binding energy into stabilizing the [tyrosine-ATP] transition state [the mutant tyrosyl-tRNA synthetase (Thr-40----Ala-40; His-45----Gly-45) has the rate of formation of tyrosyl adenylate lowered by 3.2 X 10(5) but KS for ATP is lowered by only a factor of 5]. The side chains of these residues also provide a binding site for pyrophosphate in the reverse reaction. Thus, catalysis is accomplished by stabilization of the transition state by improved binding of a group on the substrate that is distant from the seat of reaction. |
| File Format | PDF HTM / HTML |
| DOI | 10.1073/pnas.82.23.7840 |
| PubMed reference number | 3865201 |
| Journal | Medline |
| Volume Number | 82 |
| Issue Number | 23 |
| Alternate Webpage(s) | http://schultz.scripps.edu/course_references/Winter%2085.pdf |
| Alternate Webpage(s) | https://doi.org/10.1073/pnas.82.23.7840 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
